Family studies of patients with systemic lupus erythematosus have shown an increased incidence of many autoantibodies. This has included lymphocytotoxic antibody and antibodies to nucleic acids. The proposed research project will examine the function of these antibodies on several parameters of immune regulation in the family members of patients with systemic lupus erythematosus. This will utilize in vitro studies of mixed lymphocyte reactivity, HLA determination, and lymphocytotoxic antibody assays. Comprehensive family studies and studies of human household contacts of dogs with lupus will allow determinations of the role played by environmental and genetic influences on the development of overt disease in SLE patients. These results will be analyzed with respect to other known genetic markers such as ABO and Rh blood typings. Attempts will be made to define the specificity of the lymphocytotoxic antibody with respect to the antigen against which it is determined. This will utilize lymphocytes from patients with other diseases shown in previous studies to have lymphocytotoxic antibody. This will be performed by means of appropriate absorption studies prior to the assay for lymphocytotoxic antibody.